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The role of microRNA-3085 in chondrocyte function

Lookup NU author(s): Dr Matthew Barter, Professor David YoungORCiD



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


MicroRNAs have been shown to play a role in cartilage development, homeostasis and breakdown during osteoarthritis. We previously identified miR-3085 in humans as a chondrocyte-selective microRNA, however it could not be detected by Northern blot. The aim of the current study was to prove that miR-3085 is a microRNA and to investigate the function of miR-3085 in signaling pathways relevant to cartilage homeostasis and osteoarthritis. Here, we confirm that miR-3085 is a microRNA and not another class of small RNA using (1) a pre-miR hairpin maturation assay, (2) expression levels in a Dicer null cell line, and (3) Ago2 pulldown. MicroRNA-3085-3p is expressed more highly in micromass than monolayer cultured chondrocytes. Transfection of miR-3085-3p into chondrocytes decreases expression of COL2A1 and ACAN, both of which are validated as direct targets of miR-3085-3p. Interleukin-1 induces the expression of miR-3085-3p, at least in part via NFκB. In a feed-forward mechanism, miR-3085-3p then potentiates NFκB signaling. However, at early time points after transfection, its action appears to be inhibitory. MyD88 has been shown to be a direct target of miR-3085-3p and may be responsible for the early inhibition of NFκB signaling. However, at later time points, MyD88 knockdown remains inhibitory and so other functions of miR-3085-3p are clearly dominant. TGFβ1 also induces the expression of miR-3085-3p, but in this instance, it exerts a feedback inhibition on signaling with SMAD3 and SMAD4 shown to be direct targets. This in vitro analysis shows that miR-3085-3p functions in chondrocytes to induce IL-1-signaling, reduce TGFβ1 signaling, and inhibit expression of matrix genes. These data suggest that miR-3085-3p has a role in chondrocyte function and could contribute to the process of osteoarthritis.

Publication metadata

Author(s): Le L, Niu L, Barter MJ, Young DA, Dalmay T, Clark IM, Swingler TE

Publication type: Article

Publication status: Published

Journal: Scientific Reports

Year: 2020

Volume: 10

Issue: 1

Online publication date: 14/12/2020

Acceptance date: 23/11/2020

Date deposited: 12/01/2021

ISSN (electronic): 2045-2322

Publisher: Nature Publishing Group


DOI: 10.1038/s41598-020-78606-6

PubMed id: 33318505


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Funder referenceFunder name
Action Arthritis
R476/0516Dunhill Medical Trust